Apical polarity and actomyosin dynamics control Kibra subcellular localization and function in Drosophila Hippo signaling

• Published in: Developmental cell 2023-10, Vol.58 (19), p.1864-1879.e4
• Main Authors: Tokamov, Sherzod A., Nouri, Nicki, Rich, Ashley, Buiter, Stephan, Glotzer, Michael, Fehon, Richard G.
• Format: Article
• Language: English
• Subjects: actomyosin; Actomyosin - metabolism; Animals; Cell Polarity; Drosophila - metabolism; Drosophila Proteins - metabolism; epithelia; Hippo pathway; Hippo Signaling Pathway; Kibra; polarity; Protein Serine-Threonine Kinases - metabolism; Signal Transduction; tissue growth
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2023.08.029

The Hippo pathway is an evolutionarily conserved regulator of tissue growth that integrates inputs from both polarity and actomyosin networks. An upstream activator of the Hippo pathway, Kibra, localizes at the junctional and medial regions of the apical cortex in epithelial cells, and medial accumulation promotes Kibra activity. Here, we demonstrate that cortical Kibra distribution is controlled by a tug-of-war between apical polarity and actomyosin dynamics. We show that while the apical polarity network, in part via atypical protein kinase C (aPKC), tethers Kibra at the junctional cortex to silence its activity, medial actomyosin flows promote Kibra-mediated Hippo complex formation at the medial cortex, thereby activating the Hippo pathway. This study provides a mechanistic understanding of the relationship between the Hippo pathway, polarity, and actomyosin cytoskeleton, and it offers novel insights into how fundamental features of epithelial tissue architecture can serve as inputs into signaling cascades that control tissue growth, patterning, and morphogenesis. [Display omitted] •Medial actomyosin flows promote Kibra accumulation at the medial cortex•Actomyosin-driven medial Kibra assembles a Hippo signaling complex•aPKC tethers Kibra at the junctional cortex and represses its activity•A tug-of-war between apical polarity and actomyosin flows controls Hippo signaling Tokamov et al. show that apical polarity and actomyosin networks control subcellular distribution of Kibra, an activator of the growth-suppressing Hippo pathway. In a tug-of-war, apical polarity silences Kibra via junctional tethering, while actomyosin flows promote Hippo signaling via medial Kibra accumulation.